Therapeutic Potential of Curcumin for the Treatment of Brain Tumors

Brain malignancies currently carry a poor prognosis despite the current multimodal standard of care that includes surgical resection and adjuvant chemotherapy and radiation. As new therapies are desperately needed, naturally occurring chemical compounds have been studied for their potential chemotherapeutic benefits and low toxicity profile. Curcumin, found in the rhizome of turmeric, has extensive therapeutic promise via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinicalin vitroandin vivodata have shown it to be an effective treatment for brain tumors including glioblastoma multiforme. These effects are potentiated by curcumin’s ability to induce G2/M cell cycle arrest, activation of apoptotic pathways, induction of autophagy, disruption of molecular signaling, inhibition of invasion, and metastasis and by increasing the efficacy of existing chemotherapeutics. Further, clinical data suggest that it has low toxicity in humans even at large doses. Curcumin is a promising nutraceutical compound that should be evaluated in clinical trials for the treatment of human brain tumors.

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Curcumin, a Multifaceted Hormetic Agent, Mediates an Intricate Crosstalk between Mitochondrial Turnover, Autophagy, and Apoptosis

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/3656419 ◽

2020 ◽

Vol 2020 ◽

pp. 1-23 ◽

Cited By ~ 1

Author(s):

Nathan Earl Rainey ◽

Aoula Moustapha ◽

Patrice Xavier Petit

Keyword(s):

Cell Death ◽

Calcium Release ◽

Therapeutic Potential ◽

Molecular Signaling ◽

M Cell ◽

Cycle Arrest ◽

Acute Responses ◽

High Doses

Curcumin has extensive therapeutic potential because of its antioxidant, anti-inflammatory, and antiproliferative properties. Multiple preclinical studies in vitro and in vivo have proven curcumin to be effective against various cancers. These potent effects are driven by curcumin’s ability to induce G2/M cell cycle arrest, induce autophagy, activate apoptosis, disrupt molecular signaling, inhibit invasion and metastasis, and increase the efficacy of current chemotherapeutics. Here, we focus on the hormetic behavior of curcumin. Frequently, low doses of natural chemical products activate an adaptive stress response, whereas high doses activate acute responses like autophagy and cell death. This phenomenon is often referred to as hormesis. Curcumin causes cell death and primarily initiates an autophagic step (mitophagy). At higher doses, cells undergo mitochondrial destabilization due to calcium release from the endoplasmic reticulum, and die. Herein, we address the complex crosstalk that involves mitochondrial biogenesis, mitochondrial destabilization accompanied by mitophagy, and cell death.

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W436, a novel SMART derivative, exhibits anti‐hepatocarcinoma activity by inducing apoptosis and G2/M cell cycle arrest in vitro and in vivo and induces protective autophagy

Journal of Biochemical and Molecular Toxicology ◽

10.1002/jbt.22831 ◽

2021 ◽

Author(s):

Shuai Man ◽

Zhuzhu Wu ◽

Rui Sun ◽

Qi Guan ◽

Zengqiang Li ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

M Cell ◽

Cycle Arrest

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Solanum lyratumExtracts Induce Extrinsic and Intrinsic Pathways of Apoptosis in WEHI-3 Murine Leukemia Cells and Inhibit Allograft Tumor

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/254960 ◽

2012 ◽

Vol 2012 ◽

pp. 1-13 ◽

Cited By ~ 17

Author(s):

Jai-Sing Yang ◽

Chia-Chun Wu ◽

Chao-Lin Kuo ◽

Yu-Hsuan Lan ◽

Chin-Chung Yeh ◽

...

Keyword(s):

Antitumor Activity ◽

Molecular Mechanisms ◽

Fas Ligand ◽

Leukemia Cells ◽

Cycle Arrest ◽

Phase Arrest ◽

Apoptotic Pathways ◽

Murine Leukemia

We investigated the molecular mechanisms of cell cycle arrest and apoptotic death induced bySolanum lyratumextracts (SLE) or diosgenin in WEHI-3 murine leukemia cellsin vitroand antitumor activityin vivo. Diosgenin is one of the components of SLE. Our study showed that SLE and diosgenin decreased the viable WEHI-3 cells and inducedG0/G1phase arrest and apoptosis in concentration- or time-dependent manners. Both reagents increased the levels of ROS production and decreased the mitochondrial membrane potential (ΔΨm). SLE- and diosgenin-triggered apoptosis is mediated through modulating the extrinsic and intrinsic signaling pathways. Intriguingly, the p53 inhibitor (pifithrin-α), anti-Fas ligand (FasL) mAb, and specific inhibitors of caspase-8 (z-IETD-fmk), caspase-9 (z-LEHD-fmk), and caspase-3 (z-DEVD-fmk) blocked SLE- and diosgenin-reduced cell viability of WEHI-3 cells. Thein vivostudy demonstrated that SLE has marked antitumor efficacy against tumors in the WEHI-3 cell allograft model. In conclusion, SLE- and diosgenin-inducedG0/G1phase arrest and triggered extrinsic and intrinsic apoptotic pathways via p53 activation in WEHI-3 cells. SLE also exhibited antitumor activityin vivo. Our findings showed that SLE may be potentially efficacious in the treatment of leukemia in the future.

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Effect of Marsdenia tenacissima extract on G2/M cell cycle arrest by upregulating 14-3-3σ and downregulating c-myc in vitro and in vivo

Chinese Herbal Medicines ◽

10.1016/j.chmed.2019.03.002 ◽

2019 ◽

Vol 11 (2) ◽

pp. 169-176 ◽

Cited By ~ 1

Author(s):

Li Sun ◽

Qurat UI Ain ◽

Ying-sheng Gao ◽

Ghulam Jilany Khan ◽

Sheng-tao Yuan ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

M Cell ◽

Cycle Arrest ◽

Marsdenia Tenacissima

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Romidepsin Induces G2/M Phase Arrest and Apoptosis in Cholangiocarcinoma Cells

Technology in Cancer Research & Treatment ◽

10.1177/1533033820960754 ◽

2020 ◽

Vol 19 ◽

pp. 153303382096075

Author(s):

Pihong Li ◽

Luguang Liu ◽

Xiangguo Dang ◽

Xingsong Tian

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Antitumor Effect ◽

Caspase 3 ◽

M Cell ◽

Cycle Arrest ◽

Phase Arrest ◽

M Phase

Background: Cholangiocarcinoma (CCA) is an extremely intractable malignancy since most patients are already in an advanced stage when firstly discovered. CCA needs more effective treatment, especially for advanced cases. Our study aimed to evaluate the effect of romidepsin on CCA cells in vitro and in vivo and explore the underlying mechanisms. Methods: The antitumor effect was determined by cell viability, cell cycle and apoptosis assays. A CCK-8 assay was performed to measure the cytotoxicity of romidepsin on CCA cells, and flow cytometry was used to evaluate the effects of romidepsin on the cell cycle and apoptosis. Moreover, the in vivo effects of romidepsin were measured in a CCA xenograft model. Results: Romidepsin could reduce the viability of CCA cells and induce G2/M cell cycle arrest and apoptosis, indicating that romidepsin has a significant antitumor effect on CCA cells in vitro. Mechanistically, the antitumor effect of romidepsin on the CCA cell lines was mediated by the induction of G2/M cell cycle arrest and promotion of cell apoptosis. The G2/M phase arrest of the CCA cells was associated with the downregulation of cyclinB and upregulation of the p-cdc2 protein, resulting in cell cycle arrest. The apoptosis of the CCA cells induced by romidepsin was attributed to the activation of caspase-3. Furthermore, romidepsin significantly inhibited the growth of the tumor volume of the CCLP-1 xenograft, indicating that romidepsin significantly inhibited the proliferation of CCA cells in vivo. Conclusions: Romidepsin suppressed the proliferation of CCA cells by inducing cell cycle arrest through cdc2/cyclinB and cell apoptosis by targeting caspase-3/PARP both in vitro and in vivo, indicating that romidepsin is a potential therapeutic agent for CCA.

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Potential Therapeutic Targets of Quercetin, a Plant Flavonol, and Its Role in the Therapy of Various Types of Cancer through the Modulation of Various Cell Signaling Pathways

Molecules ◽

10.3390/molecules26051315 ◽

2021 ◽

Vol 26 (5) ◽

pp. 1315

Author(s):

Saleh A. Almatroodi ◽

Mohammed A. Alsahli ◽

Ahmad Almatroudi ◽

Amit Kumar Verma ◽

Abdulaziz Aloliqi ◽

...

Keyword(s):

Growth Factor ◽

Signaling Pathways ◽

Cancer Biology ◽

Therapeutic Potential ◽

Phosphatidyl Inositol ◽

Mitogen Activated Protein Kinase ◽

Molecular Signaling ◽

Anticancer Properties

Polyphenolic flavonoids are considered natural, non-toxic chemopreventers, which are most commonly derived from plants, fruits, and vegetables. Most of these polyphenolics exhibit remarkable antioxidant, anti-inflammatory, and anticancer properties. Quercetin (Qu) is a chief representative of these polyphenolic compounds, which exhibits excellent antioxidant and anticancer potential, and has attracted the attention of researchers working in the area of cancer biology. Qu can regulate numerous tumor-related activities, such as oxidative stress, angiogenesis, cell cycle, tumor necrosis factor, proliferation, apoptosis, and metastasis. The anticancer properties of Qu mainly occur through the modulation of vascular endothelial growth factor (VEGF), apoptosis, phosphatidyl inositol-3-kinase (P13K)/Akt (proteinase-kinase B)/mTOR (mammalian target of rapamycin), MAPK (mitogen activated protein kinase)/ERK1/2 (extracellular signal-regulated kinase 1/2), and Wnt/β-catenin signaling pathways. The anticancer potential of Qu is documented in numerous in vivo and in vitro studies, involving several animal models and cell lines. Remarkably, this phytochemical possesses toxic activities against cancerous cells only, with limited toxic effects on normal cells. In this review, we present extensive research investigations aimed to discuss the therapeutic potential of Qu in the management of different types of cancers. The anticancer potential of Qu is specifically discussed by focusing its ability to target specific molecular signaling, such as p53, epidermal growth factor receptor (EGFR), VEGF, signal transducer and activator of transcription (STAT), PI3K/Akt, and nuclear factor kappa B (NF-κB) pathways. The anticancer potential of Qu has gained remarkable interest, but the exact mechanism of its action remains unclear. However, this natural compound has great pharmacological potential; it is now believed to be a complementary—or alternative—medicine for the prevention and treatment of different cancers.

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Digitoxin inhibits HeLa cell growth through the induction of G2/M cell cycle arrest and apoptosis in vitro and in vivo

International Journal of Oncology ◽

10.3892/ijo.2020.5070 ◽

2020 ◽

Vol 57 (2) ◽

pp. 562-573

Author(s):

Hua Gan ◽

Ming Qi ◽

Chakpiu Chan ◽

Pan Leung ◽

Geni Ye ◽

...

Keyword(s):

Cell Cycle ◽

Cell Growth ◽

Hela Cell ◽

Cell Cycle Arrest ◽

M Cell ◽

Cycle Arrest

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Molecular Consequences of Depression Treatment: A Potential In Vitro Mechanism for Antidepressants-Induced Reprotoxic Side Effects

International Journal of Molecular Sciences ◽

10.3390/ijms222111855 ◽

2021 ◽

Vol 22 (21) ◽

pp. 11855

Author(s):

Przemysław Sołek ◽

Jennifer Mytych ◽

Anna Tabęcka-Łonczyńska ◽

Marek Koziorowski

Keyword(s):

Apoptotic Cell ◽

Neuroleptic Drug ◽

Specific Response ◽

Spermatogenic Cells ◽

M Cell ◽

In Vivo Models ◽

Cycle Arrest ◽

Venlafaxine Hydrochloride

The incidence of depression among humans is growing worldwide, and so is the use of antidepressants. However, our fundamental understanding regarding the mechanisms by which these drugs function and their off-target effects against human sexuality remains poorly defined. The present study aimed to determine their differential toxicity on mouse spermatogenic cells and provide mechanistic data of cell-specific response to antidepressant and neuroleptic drug treatment. To directly test reprotoxicity, the spermatogenic cells (GC-1 spg and GC-2 spd cells) were incubated for 48 and 96 h with amitriptyline (hydrochloride) (AMI), escitalopram (ESC), fluoxetine (hydrochloride) (FLU), imipramine (hydrochloride) (IMI), mirtazapine (MIR), olanzapine (OLZ), reboxetine (mesylate) (REB), and venlafaxine (hydrochloride) (VEN), and several cellular and biochemical features were assessed. Obtained results reveal that all investigated substances showed considerable reprotoxic potency leading to micronuclei formation, which, in turn, resulted in upregulation of telomeric binding factor (TRF1/TRF2) protein expression. The TRF-based response was strictly dependent on p53/p21 signaling and was followed by irreversible G2/M cell cycle arrest and finally initiation of apoptotic cell death. In conclusion, our findings suggest that antidepressants promote a telomere-focused DNA damage response in germ cell lines, which broadens the established view of antidepressants’ and neuroleptic drugs’ toxicity and points to the need for further research in this topic with the use of in vivo models and human samples.

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